PERIPHERAL NEUROPATHY
PHYSIOLOGY
• Pain and temperature sensation :
unmyelinated and small myelinated Ad
fibers,
• Vibratory sense, proprioception, and the
afferent limb of the tendon reflex : large
myelinated Aa and Ab fibers.
• Light touch : both large and small
myelinated fibers.
FIVE QUESTION APPROACH
1. Fiber type
2. Pattern of distribution
5. Pathology
3. Temporal course
4. Key features
• 1.What is the fiber type involved?
(motor, large sensory, small sensory, autonomic,
combination)
• 2. What is the pattern of distribution?
(distal or proximal, symmetric or asymmetric)
• 3. What is the temporal course?
(acute, chronic, progressive, stepwise, relapsing
remitting)
• 4. Are there any key features pointing to a specific
etiology? (toxic/nutritional/malignancy)
• 5. What is the pathology?
(axonal, demyelinating)
Pathological Process
• (1) Wallerian degeneration, which is the
response to axonal interruption;
• (2) Axonal degeneration or axonopathy;
• (3) Primary neuronal degeneration or
neuronopathy;
• (4) Segmental demyelination
Wallerian degeneration
• Any type of mechanical injury that
causes interruption of axons leads to
wallerian degeneration (degeneration of
axons and their myelin sheaths) distal to
the site of transection.
Axonal degeneration
• Most common pathological reaction of
peripheral nerve
• Caused by :Systemic metabolic disorders,
toxin exposure, and some inherited
neuropathies
• Also called dying-back or length-dependent
neuropathy:
• The myelin sheath breaks down along with the
axon in a process that starts at the most distal
part of the nerve fiber and progresses toward
the nerve cell body.
Dying-back neuropathy
• Clinically, presents with symmetrical, distal
loss of sensory and motor function in the lower
extremities that extends proximally in a graded
manner.
• The result is sensory loss in a stocking-like
pattern, distal muscle weakness and atrophy,
and loss of ankle reflexes
Neuronopathy
• Primary loss or destruction of nerve cell bodies with
resultant degeneration of their entire peripheral and
central axons.
• Either lower motor neurons or dorsal root ganglion cells
may be affected.
• When anterior horn cells - poliomyelitis or motor neuron
disease: focal weakness without sensory loss
• Sensory neuronopathy, or polyganglionopathy :damage
to dorsal root ganglion neurons - inability to localize the
limb in space, diffuse areflexia, and sensory ataxia.
Segmental demyelination
• The term implies injury of either myelin sheaths
or Schwann cells, resulting in breakdown of
myelin with sparing of axons
• This occurs in immune-mediated demyelinating
neuropathies and in hereditary disorders of
Schwann cell/myelin metabolism.
Demyelinating neuropathies
• Relative sparing of temperature and pinprick
sensation +
• 1.Early generalized loss of reflexes,
2.disproportionately mild muscle atrophy
3.presence of proximal and distal weakness,
4.neuropathic tremor
5. palpably enlarged nerves
Diagnostic Clues from the History
• 1.motor 2.sensory 3.autonomic disturbances.
Seek both positive and negative symptoms.
• A. Motor:
• Positive :
Muscle cramps, fasciculations, myokymia, or
tremor
• Negative :
early distal toe and ankle extensor weakness,
resulting in tripping on rugs or uneven ground
Sensory symptoms
Positive :
• prickling, searing, burning, and tight bandlike
sensations.
• Paresthesia: Unpleasant sensations arising
spontaneously without apparent stimulus
• Allodynia: perception of nonpainful stimuli as
painful.
• Hyperalgesia: Painful hypersensitivity to noxious
stimuli
• Neuropathic pain: cardinal feature of many
neuropathies.
Autonomic dysfunction
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Orthostatic lightheadedness,
Fainting spells,
Sweating reduced or excessive,
Heat intolerance,
Bladder, Bowel, and Sexual dysfunction.
Anorexia, early satiety, nausea, and vomiting
TEMPORAL CLUES
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Onset, duration, and evolution of symptoms
Tempo of disease : acute, subacute, or chronic
Course: monophasic, progressive, or relapsing
Acute presentations: Guillain-Barré syndrome
(GBS), acute porphyria, vasculitis, toxic
neuropathies.
• Relapsing course : (CIDP), acute porphyria,
Refsum's disease, hereditary neuropathy with
liability to pressure palsies (HNPP), familial
brachial plexus neuropathy, and repeated
episodes of toxin exposure.
Constitutional symptoms
•Weight loss, malaise, and anorexia.
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DM
hypothyroidism
chronic renal failure
liver disease
intestinal malabsorption
malignancy
connective tissue diseases
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[HIV]
drug use
Vitamin B6 toxicity
alcohol and dietary habits
exposure to solvents,
pesticides, or heavy
metals.
Mononeuropathy
• Focal involvement of a single nerve and
implies a local process:
• Direct trauma
• compression or entrapment
• vascular lesions
• neoplastic compression or infiltration
Mononeuropathy multiplex
• simultaneous /sequential damage to multiple
noncontiguous nerves.
• Ischemia caused by vasculitis
• Microangiopathy in diabetes mellitus
• Less common causes : Infectious,
granulomatous, leukemic, or neoplastic
infiltration, Hansen's disease (leprosy) and
sarcoidosis.
Polyneuropathy
• Characterized by symmetrical, distal motor and
sensory deficits that have a graded increase in
severity distally and by distal attenuation of
reflexes,
• Rarely predominantly proximal:(E.g: acute
intermittent porphyria).
• The sensory deficits generally follow a lengthdependent stocking-glove pattern
Motor deficits
Dominate the clinical picture in
• 1. AIDP/CIDP
• 2. Hereditary motor and sensory neuropathies,
• 3. Neuropathies associated with osteosclerotic
myeloma, porphyria, lead and organophosphate
intoxications, and hypoglycemia.
Pattern of weakness
• Asymmetrical motor weakness without
sensory loss suggests motor neuron disease or
multifocal motor neuropathy with conduction
block
Neuropathies with Facial Nerve Involvement
• Guillain-Barré syndrome
• Chronic inflammatory polyradiculoneuropathy
• Lyme disease
• Sarcoidosis
• HIV
Predominant Sensory
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Diabetes
•
Carcinoma;
Sjögren's syndrome;
Dysproteinemia;
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AIDS
vitamin B12 deficiency
Celiac disease
Toxicity with cisplatin,
thalidomide, or
pyridoxine
Inherited and idiopathic
sensory neuropathies
Autonomic dysfunction
• GBS
• Diabetes
• Amyloid sensorimotor polyneuropathy
Small-Fiber Neuropathies
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Idiopathic small fiber neuropathy
Diabetes mellitus
Amyloid neuropathy
HIV-associated distal sensory neuropathy
Hereditary sensory and autonomic neuropathies
Large-fiber
• Areflexia
• Pseudoathetosis
• Loss of joint position and vibration sense
• Positive Romberg's sign
Electrodiagnostic studies
• (1) Confirming the presence of neuropathy,
• (2) Locating focal nerve lesions,
• (3) Nature of the underlying nerve pathology
Distal motor latency prolonged
Nerve conduction velocity slow
Reduced action potential
Nerve biopsy
• In vasculitis, amyloid neuropathy, leprosy, CIDP,
Inherited disorders of myelin, and rare
axonopathies
• The Sural nerve is selected most commonly
• The superficial peroneal nerve – alternative;
:advantage of allowing simultaneous biopsy of the
peroneus brevis muscle through the same incision.
• This combined nerve and muscle biopsy
procedure increases the yield of identifying
suspected vasculitis
Neuropathies + Serum Autoantibodies
Antibodies against Gangliosides
• GM1 :
Multifocal motor neuropathy
• GM1, GD1a :
Guillain-Barré syndrome
• GQ1b :
Miller Fisher variant
Antibodies against Glycoproteins
• Myelin-associated glycoprotein :
MGUS
Antibodies against RNA-binding proteins
• Anti-Hu, antineuronal nuclear antibody 1: Malignant
inflammatory polyganglionopathy
SUMMARY
• A. Clinical pattern of neurologic findings
Polyneuropathy, Neuronopathy,
Mononeuropathy, Multiple
mononeuropathy, Plexopathies
• B. Functional disturbance: Motor, Sensory,
Autonomic, Mixed
• C. Mode of onset :
•
1.Acute 2.Subacute 3.Chronic
4.Relapsing
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• D. Pathological and electrophysiological
criteria:
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1.Demyelinating disease vs Axonopathy
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2.Wallerian degeneration - trauma
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3.Dying back neuropathy - toxic,
metabolic
• E. Etiology:
• Metabolic, immune mediated, toxic,
vasculitis, dysproteinemic, inherited,
Nutritional deficiency
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• F. Diagnosis
•
1.Clinical data
•
2.Electrophysiologic test : NCS, EMG
•
3.Biochemical test : metabolic,
nutritional,
toxic
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4.CSF study
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5. Nerve & muscle biopsy
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6. Measurement of Ig & anti-neural
antibody
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7. Genetic study